Multiple transcription factor binding sites mediate adenovirus E1A transactivation
Journal of Virology
We studied the response of simple synthetic promoter regions to transactivation by the adenovirus early region IA (ElA) protein. Binding sites for one or two host cell transcription factors were substituted for the EiB promoter region in reconstructed virus mutants, and the response to ElA transactivation was assayed during the early phase of infection. We found that a single CREB/ATF binding site resulted in a surprisingly strong promoter which responded to ElA. A CREB/ATF binding site placed
... inding site placed upstream of the E1B TATA box behaved much like the wild-type E1B promoter, which is composed of a single Spl binding site plus a TATA box. A single E2F binding site resulted in an extremely weak promoter which did not respond to ElA, much like a single Spl site. Two E2F sites in an inverted orientation with the same spacing as in the adenovirus type 2 E2 early promoter produced a strong, ElA-responsive promoter. Substitution of the E4 TATA box region for the EiB TATA box region produced a promoter about five times stronger than the wild-type E1B promoter in the absence of ElA. However, the E4 TATA box substitution did not respond significantly to ElA transactivation. These results directly demonstrate that many different transcription factor binding sites, including the ElB TATA box, a CREB/ATF binding site, and two E2F sites, can mediate ElA transactivation. Other transcription factor binding sites cannot mediate an ElA response; these other sites include the E4 TATA box, a single Spl binding site, and a single E2F binding site. Implications of these findings for the mechanism of ElA transactivation are discussed.